Heart failure in diabetes: consequences for diagnosis and therapy Arno W. Hoes, MD, PhD (no potential conflict of interest regarding this presentation) Hartfalen werkgroep, Amersfoort, Maart 2017
Pathophysiology: common pathways diabetic cardiomyopathy èlvddèhfpefèhfref hypertension coronary heart disease MacDonald M et al. Eur Heart J 2008; 29: 1224-
1. Is this an exception? Prevalence? first incidence Kenge AP et al. Progr Cardiovasc Dis 2010; 53: 45-
Prevalence HF in type 2 diabetes screening study in type 2 diabetes 605 patients 60 years or older 581 without known HF (96%) signs, symptoms ECG, chest X-ray, serum biomarkers (e.g. NTproBNP) state-of-the-art echocardiography (including tissue Doppler) newly detected HF in 161 patients (28%) HFpEF: 23%! HFrEF: 5%! Boonman-de Winter et al. Diabetologia 2012; 55:2154-
Boonman-de Winter et al. Diabetologia 2012; 55:2154-
Prevalence of previously unknown HFrEF and HFpEF stratified by age in patients with type 2 diabetes aged 60 years 50 45 40 35 30 25 20 15 10 5 0 prevalence (%) 60-64 65-69 70-74 75-80 80 Age (years) HFrEF HFpEF ALL HF Boonman-de Winter et al. Diabetologia 2012; 55:2154-
2. Diagnostic implications?
Multivariable models for predicting the presence or absence of heart failure after correction for overfitting OR (95% CI) AUC (95% CI) Model 1: Based on items from the Medical File 0.68 (0.64-0.73) Age >75 years 2.61 1.76-3.88 Female sex 1.42 0.96-2.12 History of ischaemic heart disease (IHD): 2.73 1.71-4.35 (prior MI, angina pectoris, CABG, PCI) History of hypertension 1.63 1.06-2.51 History of Transient Ischemic asack (TIA) or Stroke 1.80 0.98-3.32 History of asthma or COPD 1.61 0.93-2.80 Model 2: Medical file + symptoms 0.80 (0.76-0.83) + Dyspnoea or faygue 5.21 3.12-8.71 + Swollen ankles (reported) or nocturia 2.38 1.49-3.78 + ClaudicaYonal complaints 3.14 1.46-6.78 + Cardiac palpitayons 1.45 0.87-2.41 Model 3: Clinical Model :File, symptoms and signs 0.82 (0.79-0.86) + Pulmonary crepitayons, elevated jugular pressure, 3.08 1.98-4.80 peripheral oedema, hepatomegaly (signs of water and salt retenyon) Model 4: Clinical model + NT-proBNP 0.84 (0.81-0.88) + NT-proBNP >15pmol/l 3.17 1.95-5.16 Model 5: Clinical model + abnormal ECG 0.85 (0.82-0.88) + An abnormal ECG 3.86 2.28-6.53 Model 6: Clinical model + NT-pro BNP and ECG 0.86 (0.83-0.89) + NT-proBNP >15pmol/Ll ( 125 pg/ml) 2.70 1.63-4.48 + Abnormal ECG 3.39 1.98-5.80 Boonman-de Winter et al. submitted
3. Prognostic implications A total of 68 of the 187 patients (36.4%) died during the 12-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%.
Prognostic implications: real patients no HF HFpEF HFrEF Boonman-de Winter et al.int J Cardiol;2015:185:162-
4. HF therapy different in those with diabetes? HFrEF! Ponikowski et al. EHJ doi:10.1093/eurheartj/ehw128
Diuretics no RCTs with morbidity/mortality outcome (ever) in case of volume overload loop diuretics instead of thiazides Ryden et al. Eur Heart J 34, 3035-
ACE-inhibition Beware of subgroup analyses! Shekelle PG et al. JACC 2003; 41: 1529-
Betablockers more side effects in diabetes (hypoglycaemia), especially in non-selective beta-blockers no doubt: advantages outweight the risks Shekelle PG et al. JACC 2003; 41: 1529-
Are betablockers less effective in diabetes? SENIORS: Elderly patients with HFrEF on nebivolol Effect on mortality or CV hospital admission Flather et al. EHJ 2005
MRAs: even more effective in diabetes? Eschalier et al. JACC 2013
Standard HFrEF therapy in diabetes diuretics: prescribe loop diuretics when needed ACE-inhibitors (ARBs): effective betablockers: effective (maybe less effective?) MRAs: effective the rest: also effective (we believe)
And what about the ARNIs?
Remember the study in Zeeland? 31% heart failure (of which 87% unknown) unknown heart failure: 83% HF-pEF!!! Boonman-de Winter et al, Diabetologia 2012;55:2154 HFpEF! Ponikowski et al. EHJ doi:10.1093/eurheartj/ehw128
5. Diabetes therapy different in those with HF? Gi# AK et al. Eur J Heart Fail 2012; 14; 1389-
Metformin NO TRIALS ( ever ) lactic acidoses? Eurich et al. Circulation HF 2013
Sulfonylurea NO TRIALS not contraindicated but caution, because of hypoglycaemia risk Eurich et al. Circ Heart Fail. 2013;6:395-
Insulin beneficial effects? (eg positive inotropic, myocardial glucose uptake) Murcia et al. Arch Intern Med. 2004;164:2273- Masoudi et al. Circulation 2005;111:583-
Thiazolidinediones Dargie et al. JACC 2007; 49:1696-
DPP4-inhibitors, GLP-1 agonists? not first (or second or third) choice in diabetes limited evidence of effect in HF/diabetes patients no evident problems (yet?) some better than SUs or insulin?
SGLT-2 inhibitors: beneficial?
SGLT-2 inhibitors: beneficial? But: only 10% had heart failure!
Standard antidiabetic therapy in HF? metformin: drug of choice in HF insulin, sulphonylureas: caution, not contra-indicated thiazolidinediones: contra-indicated GLP-1 agonists, DPP-4-inhibitors? SGLT-2 inhibitors beneficial?
6. Should we more actively look for HF in diabetes? ample opportunity: routine visits very high prevalence (30% in 60 plus) poorer prognosis when also HF however: many HFpEF with no effective therapy in case of HFrEF: effective treatment
And what do the guidelines say? Guideline screening for: CV disease heart failure NICE 2009 no, only CV risk no EAD 2012 no no ESC-EASD 2013 no, just CV risk no ADA 2014, 2016 no, just CV risk no Dutch GPs, 2013 yes yes?
Should we screen for HF in diabetes? Screening for HFrEF? No screening for HFpEF? Boonman-de Winter et al. Neth J Med 2016
Heart failure in diabetes very high prevalence of unknown HF: 5% HFrEF; 23% HFpEF diagnosis HF: similar as in those without diabetes therapy HF: almost similar loop diuretics; betablockers? therapy diabetes: some differences no thiazolidinediones; SUs, insulin careful?; SGLT2-antagonists? more active screening for HF in clinical practice